Arrhythmia and Death Following Percutaneous Revascularization in Ischemic Left Ventricular Dysfunction: Prespecified Analyses From the REVIVED-BCIS2 Trial.

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; P=0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01920048.

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

BACKGROUND: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. METHODS: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. RESULTS: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. CONCLUSIONS: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Wave speed in human coronary arteries is not influenced by microvascular vasodilation: implications for wave intensity analysis.

Wave intensity analysis and wave separation are powerful tools for interrogating coronary, myocardial and microvascular physiology. Wave speed is integral to these calculations and is usually estimated by the single-point technique (SPc), a feasible but as yet unvalidated approach in coronary vessels. We aimed to directly measure wave speed in human coronary arteries and assess the impact of adenosine and nitrate administration. In 14 patients, the transit time Δt between two pressure signals was measured in angiographically normal coronary arteries using a microcatheter equipped with two high-fidelity pressure sensors located Δs = 5 cm apart. Simultaneously, intracoronary pressure and flow velocity were measured with a dual-sensor wire to derive SPc. Actual wave speed was calculated as DNc = Δs/Δt. Hemodynamic signals were recorded at baseline and during adenosine-induced hyperemia, before and after nitroglycerin administration. The energy of separated wave intensity components was assessed using SPc and DNc. At baseline, DNc equaled SPc (15.9 ± 1.8 vs. 16.6 ± 1.5 m/s). Adenosine-induced hyperemia lowered SPc by 40 % (p < 0.005), while DNc remained unchanged, leading to marked differences in respective separated wave energies. Nitroglycerin did not affect DNc, whereas SPc transiently fell to 12.0 ± 1.2 m/s (p < 0.02). Human coronary wave speed is reliably estimated by SPc under resting conditions but not during adenosine-induced vasodilation. Since coronary wave speed is unaffected by microvascular dilation, the SPc estimate at rest can serve as surrogate for separating wave intensity signals obtained during hyperemia, thus greatly extending the scope of WIA to study coronary physiology in humans.

Synergistic adaptations to exercise in the systemic and coronary circulations that underlie the warm-up angina phenomenon.

BACKGROUND: The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. METHODS AND RESULTS: Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (P<0.01). A 33% decline in aortic pressure augmentation in Ex2 (P<0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (P<0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P<0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (P<0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. CONCLUSIONS: On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular-ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.

Appearance of microvascular obstruction on high resolution first-pass perfusion, early and late gadolinium enhancement CMR in patients with acute myocardial infarction.

BACKGROUND: The presence and extent of microvascular obstruction (MO) after acute myocardial infarction can be measured by first-pass gadolinium-enhanced perfusion cardiovascular magnetic resonance (CMR) or after gadolinium injection with early or late enhancement (EGE/LGE) imaging. The volume of MO measured by these three methods may differ because contrast agent diffusion into the MO reduces its apparent extent over time. Theoretically, first-pass perfusion CMR should be the most accurate method to measure MO, but this technique has been limited by lower spatial resolution than EGE and LGE as well as incomplete cardiac coverage. These limitations of perfusion CMR can be overcome using spatio-temporal undersampling methods. The purpose of this study was to compare the extent of MO by high resolution first-pass k-t SENSE accelerated perfusion, EGE and LGE. METHODS: 34 patients with acute ST elevation myocardial infarction, treated successfully with primary percutaneous coronary intervention (PPCI), underwent CMR within 72 hours of admission. k-t SENSE accelerated first-pass perfusion MR (7 fold acceleration, spatial resolution 1.5 mm x 1.5 mm x 10 mm, 8 slices acquired over 2 RR intervals, 0.1 mmol/kg Gd-DTPA), EGE (14 minutes after injection with a fixed TI of 440 ms) and LGE images (1012 minutes after injection, TI determined by a Look-Locker scout) were acquired. MO volume was determined for each technique by manual planimetry and summation of discs methodology. RESULTS: k-t SENSE first-pass perfusion detected more cases of MO than EGE and LGE (22 vs. 20 vs. 14, respectively). The extent of MO imaged by first-pass perfusion (median mass 4.7 g, IQR 6.7) was greater than by EGE (median mass 2.3 g, IQR 7.1, p = 0.002) and LGE (median mass 0.2 g, IQR 2.4, p = 0.0003). The correlation coefficient between MO mass measured by first-pass perfusion and EGE was 0.91 (p < 0.001). CONCLUSION: The extent of MO following acute myocardial infarction appears larger on high-resolution first-pass perfusion CMR than on EGE and LGE. Given the inevitable time delay between gadolinium administration and acquisition of either EGE or LGE images, high resolution first-pass perfusion imaging may be the most accurate method to quantify MO.

Deleterious Effects of Cold Air Inhalation on Coronary Physiological Indices in Patients With Obstructive Coronary Artery Disease.

Background Cold air inhalation during exercise increases cardiac mortality, but the pathophysiology is unclear. During cold and exercise, dual-sensor intracoronary wires measured coronary microvascular resistance ( MVR ) and blood flow velocity ( CBF ), and cardiac magnetic resonance measured subendocardial perfusion. Methods and Results Forty-two patients (62±9 years) undergoing cardiac catheterization, 32 with obstructive coronary stenoses and 10 without, performed either (1) 5 minutes of cold air inhalation (5°F) or (2) two 5-minute supine-cycling periods: 1 at room temperature and 1 during cold air inhalation (5°F) (randomized order). We compared rest and peak stress MVR , CBF , and subendocardial perfusion measurements. In patients with unobstructed coronary arteries (n=10), cold air inhalation at rest decreased MVR by 6% ( P=0.41), increasing CBF by 20% ( P<0.01). However, in patients with obstructive stenoses (n=10), cold air inhalation at rest increased MVR by 17% ( P<0.01), reducing CBF by 3% ( P=0.85). Consequently, in patients with obstructive stenoses undergoing the cardiac magnetic resonance protocol (n=10), cold air inhalation reduced subendocardial perfusion ( P<0.05). Only patients with obstructive stenoses performed this protocol (n=12). Cycling at room temperature decreased MVR by 29% ( P<0.001) and increased CBF by 61% ( P<0.001). However, cold air inhalation during cycling blunted these adaptations in MVR ( P=0.12) and CBF ( P<0.05), an effect attributable to defective early diastolic CBF acceleration ( P<0.05) and associated with greater ST -segment depression ( P<0.05). Conclusions In patients with obstructive coronary stenoses, cold air inhalation causes deleterious changes in MVR and CBF . These diminish or abolish the normal adaptations during exertion that ordinarily match myocardial blood supply to demand.

The CTSA Consortium's Catalog of Assets for Translational and Clinical Health Research (CATCHR).

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortium's effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open-access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web-based tool. Additional easy-to-use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources.

Assessment of coronary artery stenosis severity and location: quantitative analysis of transmural perfusion gradients by high-resolution MRI versus FFR.

OBJECTIVES: This study sought to test the hypothesis that transmural perfusion gradients (TPG) on adenosine stress myocardial perfusion cardiac magnetic resonance (CMR) predict hemodynamically significant coronary artery disease (CAD) as defined by fractional flow reserve (FFR). BACKGROUND: Myocardial ischemia affects the subendocardial layers of the left ventricular myocardium earlier and more severely than the outer layers, and the identification of TPG should be sensitive and specific for the diagnosis of CAD. Previous studies have shown that high spatial resolution myocardial perfusion CMR allows quantitation of TPG between the subendocardium and the subepicardium. METHODS: Sixty-seven patients (53 men, age 61 ± 9 years) underwent coronary angiography and high-resolution (1.2 × 1.2-mm in-plane) adenosine stress perfusion CMR at 3.0-T. TPG was calculated for 3 coronary territories. Visual analysis was performed to identify myocardial ischemia. FFR was measured in all vessels with ≥50% severity stenosis. FFR <0.8 was considered hemodynamically significant. In a training group of 30 patients, the optimal threshold of TPG to detect significant CAD was determined (Group 1). This threshold was then tested prospectively in the remaining 37 patients (Group 2). RESULTS: In Group 1, a 20% TPG provided the best diagnostic threshold on both per-segment and per-patient analysis. Applied to Group 2, this threshold yielded a sensitivity of 0.78, specificity of 0.94, and area under the curve of 0.86 for the detection of CAD in a per-segment analysis and of 0.89, 0.83, and 0.86 in a per-patient analysis, respectively. TPG had a similar diagnostic accuracy to visual assessment. Linear regression analysis showed a relationship between TPG and FFR values, with r = 0.63 (p < 0.001). CONCLUSIONS: The quantitative analysis of transmural perfusion gradients on high-resolution myocardial perfusion CMR accurately predicts hemodynamically significant CAD as defined by FFR. A TPG diagnostic threshold of 20% is as accurate as visual assessment.

Does the instantaneous wave-free ratio approximate the fractional flow reserve?

OBJECTIVES: This study sought to examine the clinical performance of and theoretical basis for the instantaneous wave-free ratio (iFR) approximation to the fractional flow reserve (FFR). BACKGROUND: Recent work has proposed iFR as a vasodilation-free alternative to FFR for making mechanical revascularization decisions. Its fundamental basis is the assumption that diastolic resting myocardial resistance equals mean hyperemic resistance. METHODS: Pressure-only and combined pressure-flow clinical data from several centers were studied both empirically and by using pressure-flow physiology. A Monte Carlo simulation was performed by repeatedly selecting random parameters as if drawing from a cohort of hypothetical patients, using the reported ranges of these physiologic variables. RESULTS: We aggregated observations of 1,129 patients, including 120 with combined pressure-flow data. Separately, we performed 1,000 Monte Carlo simulations. Clinical data showed that iFR was +0.09 higher than FFR on average, with ±0.17 limits of agreement. Diastolic resting resistance was 2.5 ± 1.0 times higher than mean hyperemic resistance in patients. Without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Nearly identical scatter of iFR versus FFR was seen between simulation and patient observations, thereby supporting our model. CONCLUSIONS: iFR provides both a biased estimate of FFR, on average, and an uncertain estimate of FFR in individual cases. Diastolic resting myocardial resistance does not equal mean hyperemic resistance, thereby contravening the most basic condition on which iFR depends. Fundamental relationships of coronary pressure and flow explain the iFR approximation without invoking wave mechanics.

High-resolution magnetic resonance myocardial perfusion imaging at 3.0-Tesla to detect hemodynamically significant coronary stenoses as determined by fractional flow reserve.

OBJECTIVES: The objective of this study was to compare visual and quantitative analysis of high spatial resolution cardiac magnetic resonance (CMR) perfusion at 3.0-T against invasively determined fractional flow reserve (FFR). BACKGROUND: High spatial resolution CMR myocardial perfusion imaging for the detection of coronary artery disease (CAD) has recently been proposed but requires further clinical validation. METHODS: Forty-two patients (33 men, age 57.4 ± 9.6 years) with known or suspected CAD underwent rest and adenosine-stress k-space and time sensitivity encoding accelerated perfusion CMR at 3.0-T achieving in-plane spatial resolution of 1.2 × 1.2 mm(2). The FFR was measured in all vessels with >50% severity stenosis. Fractional flow reserve <0.75 was considered hemodynamically significant. Two blinded observers visually interpreted the CMR data. Separately, myocardial perfusion reserve (MPR) was estimated using Fermi-constrained deconvolution. RESULTS: Of 126 coronary vessels, 52 underwent pressure wire assessment. Of these, 27 lesions had an FFR <0.75. Sensitivity and specificity of visual CMR analysis to detect stenoses at a threshold of FFR <0.75 were 0.82 and 0.94 (p < 0.0001), respectively, with an area under the receiver-operator characteristic curve of 0.92 (p < 0.0001). From quantitative analysis, the optimum MPR to detect such lesions was 1.58, with a sensitivity of 0.80, specificity of 0.89 (p < 0.0001), and area under the curve of 0.89 (p < 0.0001). CONCLUSIONS: High-resolution CMR MPR at 3.0-T can be used to detect flow-limiting CAD as defined by FFR, using both visual and quantitative analyses.

Interleaved T(1) and T(2) relaxation time mapping for cardiac applications.

PURPOSE: To diagnose acute myocardial infarction (MI) with MRI, T(1)-weighted and T(2)-weighted images are required to detect necrosis and edema. The calculation of both T(1) and T(2) maps can be relevant for quantitative diagnosis. In this work, we present a simultaneous quantification of T(1)-T(2) relaxation times of a short-axis view of the heart in a single scan. MATERIALS AND METHODS: An electrocardiograph (ECG)-triggered, navigator-gated, interleaved T(1) and T(2) mapping sequence was implemented for the quantification of the T(1) and T(2) values of phantoms, healthy volunteers, and three patients with acute MI. The proposed acquisition scheme consisted of an interleaved two-dimensional (2D) steady-state free precession (SSFP) sequence with three different modules: an inversion-recovery (IR) sequence with multiple time delays, followed by a delay of one cardiac cycle for magnetization recovery and a T(2)-preparation pulse with multiple echo-times for T(2) quantification. RESULTS: Measurements of in vivo relaxation times were in good agreement with literature values. The interleaved sequence was able to measure T(1) and T(2) relaxation times of the myocardium. CONCLUSION: The interleaved sequence acquires data for the calculation of T(1) and T(2) maps in only one scan without the need for registration. This technique has the potential to differentiate between acute and chronic MI by estimating the concentration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in the necrotic tissue and to assess the extent of edema from T(2) maps.

Three-dimensional analysis of vulnerable segments in the left anterior descending artery.

OBJECTIVES: Analysis of conventional angiograms has suggested that specific anatomic parameters of particular segments of a coronary artery render them prone to vulnerable plaque development, plaque rupture, and consequent thrombosis. This study aimed at performing a three-dimensional analysis of recanalized left anterior descending (LAD) coronary arteries in patients who had suffered an anterior ST-elevation myocardial infarction (STEMI). METHODS: Coronary angiograms of 76 consecutive patients with an anterior STEMI and a recanalized LAD were reconstructed in the three-dimensional space, and compared with angiograms of 76 patients with stable coronary artery disease (SCAD) and significant LAD stenosis. RESULTS: In both groups the majority of lesions occurred between 20 and 40 mm (P=0.745), but the number of lesions beyond 60 mm from the ostium was significantly higher in SCAD compared with STEMI (P=0.045). Culprit lesions were statistically significantly longer in patients with STEMI compared with SCAD (18.3+/-7.5 vs. 12.7+/-6.2 mm, P<0.001). Cut-off point analysis indicated a lesion length of >or=12.5 mm as discriminating threshold between SCAD and STEMI (sensitivity 79% and specificity 63%). Bifurcation branches on the culprit lesion were seen in 79% of the patients with STEMI and 58% of those with SCAD (P=0.026). Lesion angulation was significantly sharper in STEMI compared with SCAD patients in diastole (155+/-15 vs. 160+/-14 degrees, P=0.037). Multiple logistic regression model including these parameters had a high discriminating ability with c-statistic 0.78 (95% confidence intervals: 0.71-0.86), sensitivity 72.4%, and specificity 75%. CONCLUSION: Specific anatomic characteristics of LAD segments predispose to development of plaque rupture and thrombosis.